ich-q9质量风险.doc

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1、-作者xxxx-日期xxxxICH-Q9质量风险管理【精品文档】INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE人用药注册技术要求国际协调会议ICH Harmonised Tripartite Guideline人用药注册技术要求国际协调会议三方协调后的指南Quality Risk Management质量风险管理Current Step 4 version现行第四步版本dated 9 November 200

2、52005 年十一月 9日This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European

3、 Union, Japan and USA.本指南由人用药注册技术要求国际协调会议专家工作组根据人用药注册技术要求国际协调会议程序开发并提交各方的药政部门咨询。根据人用药注册技术要求国际协调会议程序第四步，推荐给欧盟、日本和美国药的政部门采用的最终文本。Document History文件历史Codification最初编码History历史Approval by the Steering Committee under Step 2 and release for public consultation.指导委员会批准第二步文件并发放用于公开咨询Date日期Q922 March 200520

4、05 / 3 /22Approval by the Steering Committee of Post Step 2 correction指导委员会在批准第二步后的订正文件15 June 20052005/ 6 / 15Current Step 4 version现行第四步版本Approval by the Steering Committee under Step 4 and recommendation for adoption to the three ICH regulatory bodies.指导委员会批准第四步文件并推荐 ICH 三方药政部门批准9 November 200520

5、05 / 11 / 9Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 9 November 2005, this guideline is recommended for adoption to the three regulatory parties to ICH在 2005 年 11 月 9 日的人用药注册技术要求国际协调会议上，本指南已经通过人用药注册技术要求国际协调会议第四步程序，本指南已经推荐给人用药注册技术要求国际协调会议三方的药政部门采用。TABLE OF CONT

6、ENTS目录1. INTRODUCTION 简介.12. SCOPE 范围.23. PRINCIPLES OF QUALITY RISK MANAGEMENT 质量风险管理的原则.24. GENERAL QUALITY RISK MANAGEMENT PROCESS 常规质量风险管理程序.24.1 Responsibilities 职责.44.2 Initiating a Quality Risk Management Process 启动质量风险管理过程.44.3 Risk Assessment 风险评估.44.4 Risk Control风险控制.54.5 Risk Communicati

7、on风险沟通.64.6 Risk Review 风险评审.65. RISK MANAGEMENT METHODOLOGY 风险管理方法学 .76. INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY AND REGULATORY OPERATIONS质量风险管理与业界及药政运行整合.87. DEFINITIONS 定义.98. REFERENCES 参考文献.11Annex 附录 I: Risk Management Methods and Tools风险管理方法与工具. 12I.1 Basic Risk Management Facili

8、tation Methods基本风险管理简易方法 . 12I.2 Failure Mode Effects Analysis故障模式效应分析(FMEA).12I.3 Failure Mode, Effects and Criticality Analysis 故障模式影响与严重性分析(FMECA).13I.4 Fault Tree Analysis 故障树分析(FTA).13I.5 Hazard Analysis and Critical Control Points危害分析关键控制点(HACCP).14I.6 Hazard Operability Analysis 危害及可操作性分析(HAZ

9、OP).14I.7 Preliminary Hazard Analysis 预先危险分析(PHA).15I.8 Risk Ranking and Filtering风险排序及过滤 .15I.9 Supporting Statistical Tools辅助性统计工具.16Annex 附录 II: Potential Applications for Quality Risk Management 实施质量风险管理的潜在机会.16II.1 Quality Risk Management as Part of Integrated Quality Management 整合质量管理部分的质量风险管理

10、.16II.2 Quality Risk Management as Part of Regulatory Operations 药政操作部分的质量风险管理.18II.3 Quality Risk Management as Part of development 开发部分的质量风险管理 .19II.4 Quality Risk Management for Facilities, Equipment and Utilities 厂房，设备和公用设施的质量风险管理 .19II.5 Quality Risk Management as Part of Materials Management 物

11、料管理部分的质量风险管理.21II.6 Quality Risk Management as Part of Production 生产部分的质量风险管理.21II.7 Quality Risk Management as Part of Laboratory Control and Stability Studies 实验室控制和稳定性研究部分的质量Quality Risk Management质量风险管理风险管理.22II.8 Quality Risk Management as Part of Packaging and Labelling 包装和标签部分的质量风险管理.221. INT

12、RODUCTION 导言Risk management principles are effectively utilized in many areas of business and government including finance, insurance, occupational safety, public health, pharmacovigilance, and by agencies regulating these industries. Although there are some examples of the use of quality risk manag

13、ement in the pharmaceutical industry today, they are limited and do not represent the full contributions that risk management has to offer. In addition, the importance of quality systems has been recognized in the pharmaceutical industry and it is becoming evident that quality risk management is a v

14、aluable component of an effective quality system.风险管理原则被有效地应用于许多商业和政府的领域，包括金融、保险、职业安全、公共健康、药物预警，以及这些行业的主管部门。如今，尽管在制药行业也有一些运用质量风险管理的例子，但其非常有限，且没有体现出风险管理能提供的全部贡献。另外，制药行业已经认识到质量体系的重要性，而且，质量风险管理对一个有效的质量体系来说，是一个有价值的组成部分这一点越来越明显。It is commonly understood that risk is defined as the combination of the prob

15、ability of occurrence of harm and the severity of that harm. However, achieving a shared understanding of the application of risk management among diverse stakeholders is difficult because each stakeholder might perceive different potential harms, place a different probability on each harm occurring

16、 and attribute different severities to each harm. In relation to pharmaceuticals, although there are a variety of stakeholders, including patients and medical practitioners as well as government and industry, the protection of the patient by managing the risk to quality should be considered of prime

17、 importance.通常将风险理解为，风险是由伤害发生的概率及伤害严重性结合而成。然而，在不同的风险涉众中达成对风险管理应用共识仍是困难的，因为每个风险涉众可能感觉到不同的潜在伤害，对每个所发生的伤害设置不同的概率以及伤害不同的严重性属性。对于药品来说，尽管有多种的风险涉众，包括患者、医疗从业人员，以及政府和业界，运用质量风险管理都应该以保护病人为基本出发点。The manufacturing and use of a drug (medicinal) product, including its components, necessarily entail some degree of

18、risk. The risk to its quality is just one component of the overall risk. It is important to understand that product quality should be maintained throughout the product lifecycle such that the attributes that are important to the quality of the drug (medicinal) product remain consistent with those us

19、ed in the clinical studies. An effective quality risk management approach can further ensure the high quality of the drug (medicinal) product to the patient by providing a proactive means to identify and control potential quality issues during development and manufacturing. Additionally, use of qual

20、ity risk management can improve the decision making if a quality problem arises. Effective quality risk management can facilitate better and more informed decisions, can provide regulators with greater assurance of a companys ability to deal with potential risks and can beneficially affect the exten

21、t and level of direct regulatory oversight.药物(医疗)产品制造和使用，包括它的组份，必然要承担一定程度的风险。其质量风险仅是全部风险中的一个。重要的是要了解到，产品质量应当贯穿产品的生命周期，这个属性对于药物(医疗)产品保持与临床研究时一致是非常重要的。通过前瞻意义上辨识与控制在研发与制造中的潜在质量问题，一个有效的质量风险管理方法能进一步给患者提供高质量药物(医疗)产品质量的保证。另外，如果出现质量问题，则采用质量风险管理可以改善决策。有效的质量风险管理可以促使做出更好，更基于可靠信息的决策，可以为业界药政部门提供更强大应对潜在风险的能力的保证，并

22、且会对药政监督的水平和范围直接产生有利影响。The purpose of this document is to offer a systematic approach to quality risk management. It serves as a foundation or resource document that is independent of, yet supports, other ICH Quality documents and complements existing quality practices, requirements, standards, and g

23、uidelines within the pharmaceutical industry and regulatory environment. It specifically provides guidance on the principles and some of the tools of quality risk management that can enable more effective and consistent risk based decisions, both by regulators and industry, regarding the quality of

24、drug substances and drug (medicinal) products across the product lifecycle. It is not intended to create any new expectations beyond the current regulatory requirements.本文件的目的是提供一个质量风险管理的综合方法。其作为一个基础的或资源性的文件，其独立并支撑其它的ICH 质量文件，并对现有的质量实践、要求、标准以及制药行业指南与药政环境进行补充。其将明确提供质量风险管理的原理，以及一些工具，其可以确保在药政部门和业界在考虑到贯

25、穿在整个产品生命周期的原料药和药物(医疗)产品质量时，做出更有效与更一致的基于风险的决策。其并未试图建立任何超越当前管理要求的新的要求。It is neither always appropriate nor always necessary to use a formal risk management process (using recognized tools and/ or internal procedures e.g., standard operating procedures). The use of informal risk management processes (u

26、sing empirical tools and/ or internal procedures) can also be considered acceptable. Appropriate use of quality risk management can facilitate but does not obviate industrys obligation to comply with regulatory requirements and does not replace appropriate communications between industry and regulat

27、ors.使用一个正式的风险管理过程(使用公认的工具，和/或内部程序，例如标准操作程序)既不总是恰当的，也不总是必须的。采用非正式的风险管理过程(使用经验的工具，和/或内部程序)也是可以考虑接受。恰当运用质量风险管理可以促进，但并不能免除业界遵守药政要求的责任，也不能取代业界和药政部门之间适当的沟通。2. SCOPE 范围This guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceut

28、ical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances, drug (medicinal) products, biological and biotechnological products (including the use of raw materials, solvents, excipients,

29、 packaging and labeling materials in drug (medicinal) products, biological and biotechnological products).本指南给出了质量风险管理的原理以及一些工具的例子，其可以应用于药品质量的不同方面。这些方面包括开发、制造、分销以及原料药、药物(医疗)产品、生物和生物技术产品(包括在药物(医疗)产品、生物和生物技术产品中使用到的原料、溶剂、赋形剂、包装和标签材料) 整个生命周期的检查和注册/评审过程。3. PRINCIPLES OF QUALITY RISK MANAGEMENT 质量风险管理的原则T

30、wo primary principles of quality risk management are:质量风险管理的两个基本原则为： The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient; and应该基于科学知识和最终与对患者的保护相关联对质量风险进行评价；以及 The level of effort, formality and documentation of the qualit

31、y risk management process should be commensurate with the level of risk.质量风险管理过程的力度、正式程度和文件化程度都应该与风险水平相适应。4. GENERAL QUALITY RISK MANAGEMENT PROCESS 常规质量风险管理程序Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the drug (me

32、dicinal) product across the product lifecycle. A model for quality risk management is outlined in the diagram (Figure 1). Other models could be used. The emphasis on each component of the framework might differ from case to case but a robust process will incorporate consideration of all the elements

33、 at a level of detail that is commensurate with the specific risk.质量风险管理指的是对贯穿于药物(医疗)产品生产周期中的风险进行评估、控制、沟通及评审的系统过程。图中概括了质量风险管理模式(图 1)。也可以使用其他模式。所强调的构架中每个组成，可依不同情况而有所不同的，但一个完善的过程会更加详细地整合考虑到所有因素，其与具体的风险有相同的水平。Figure 1: Overview of a typical quality risk management process图 1：典型的质量风险管理过程概述unacceptable不接

34、受Risk Review 风险评审Risk Control 风险控制Initiate Quality Risk Management Process启动风险管理过程风险控制Risk Reduction 风险降低Risk Acceptance 接受风险Output / Result of the Quality Risk Management Process质量风险管理程序的输出/结果风险控制Review Events 事件评审Risk Communication 风险沟通Risk Management tools 风险管理工具Risk Assessment 风险评估Risk Identific

35、ation 风险辩识Analysis Risk 风险分析Risk Evaluationun 风险评价 Decision nodes are not shown in the diagram above because decisions can occur at any point in the process. These decisions might be to return to the previous step and seek further information, to adjust the risk models or even to terminate the risk

36、management process based upon information that supports such a decision. Note: “unacceptable” in the flowchart does not only refer to statutory, legislative or regulatory requirements, but also to the need to revisit the risk assessment process.在上图中并未标明判断结点，因为判断可出现在这个过程中的任何一个点。这些判断将会退回到前一步，并寻求进一步的信息

37、以调整风险模型，甚至根据支持这个判断的信息来终止风险管理过程。（注：在流程图中的“不接受”不仅仅是依据法定、立法或药政要求，同样也需要返回风险评估过程。）4.1 Responsibilities职责Quality risk management activities are usually, but not always, undertaken by interdisciplinary teams. When teams are formed, they should include experts from the appropriate areas (e.g., quality unit,

38、 business development, engineering, regulatory affairs, production operations, sales and marketing, legal, statistics and clinical) in addition to individuals who are knowledgeable about the quality risk management process.风险管理活动通常，但并不总是，需要多学科的团队参与。当形成一个团队时，应当要包括适当领域的专家(例如，质量部门、商业开发、工程、药政、生产运行、销售和市场

39、、法律和临床)，及精通质量风险管理过程的个人。Decision makers should 决策者应当： take responsibility for coordinating quality risk management across various functions and departments of their organization; and负责在其组织内各职能部门间协调质量风险管理；以及， assure that a quality risk management process is defined, deployed and reviewed and that adeq

40、uate resources are available.确保明确，开展与评审了质量风险管理过程，并有适当的资源。4.2 Initiating a Quality Risk Management Process 启动质量风险管理过程Quality risk management should include systematic processes designed to coordinate, facilitate and improve science-based decision making with respect to risk. Possible steps used to in

41、itiate and plan a quality risk management process might include the following:质量风险管理包括那些用于协调、促进和改善做出与风险相关的基于科学的决策系统过程。可能用于启动和策划一个质量风险管理过程的步骤可能包括以下几点： Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk;明确问题和/或风险问题，包括辨识潜在风险相关假设； Assemble backgro

42、und information and/ or data on the potential hazard, harm or human health impact relevant to the risk assessment;收集与风险评估相关的潜在危险、伤害或影响人体健康的背景信息和资料和/或数据； Identify a leader and necessary resources; 辩识领导与必要的资源； Specify a timeline, deliverables and appropriate level of decision making for the risk manag

43、ement process.指定风险管理程序的时限、交付日期与决策水平。4.3 Risk Assessment 风险评估Risk assessment: consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards (as defined below). Quality risk assessments begin with a well-defined problem description or risk question. When the risk in question is well defined, an appropriate risk management tool (see examples in section 5) and the types of information needed to address